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- Herland, Anna, 1979-
(författare)
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Conjugated Polymers, Amyloid Detection and Assembly of Biomolecular Nanowires
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The research field of conjugated polymers has grown due to the optical and electronic properties of the material, useful in applications such as solar cells and printed electronics, but also in biosensors and for interactions with biomolecules. In this thesis conjugated polymers have been used in two related topics; to detect conformational changes in proteins and to assemble the polymers with biomolecules into nanowires.Within biosensing, conjugated polymers have been used for detection of a wide range of biological events, such as DNA hybridization or enzymatic activity, utilizing both electronic and optical changes in the polymer. Here the focus has been to use the polymers as optical probes to discriminate between native and misfolded protein, as well as to follow the misfolding processes in vitro. The understanding and detection of protein misfolding, for example amyloid fibril formation, is a topic of growing importance. The misfolding process is strongly associated with several devastating diseases such as Alzheimer’s disease, Parkinson’s disease and Bovine Spongiform Encephalopathy (BSE). We have developed detection schemes for discrimination between proteins in the native or amyloid fibril state based on luminescent polythiophene derivatives. Through a synthesis strategy based on polymerization of trimer blocks rather than of monomers, polythiophene derivatives with higher optical signal specificity for amyloid-like fibrils were obtained.Self-assembly of nanowires containing conjugated polymers is a route to generate structures of unique opto-electrical characteristics without the need for tedious topdown processes. Biomolecules can have nanowire geometries of extraordinary aspect ratio and functionalities. The DNA molecule is the most well known and exploited of these. In this thesis work the more stable amyloid fibril has been used as a template to organize conjugated polymers. Luminescent, semi-conducting, conjugated polymers have been incorporated in and assembled onto amyloid fibrils. Using luminescence quenching we have demonstrated that the conjugated material can retain the electro-activity after the incorporation process. Furthermore, the amyloid fibril/conjugated polymer hybrid structures can be organized on surfaces by the means of molecular combing and soft lithography.In the process of generating self-assembled biomolecular nanowires functionalized with conjugated polymers, we have shown a new synthesis strategy for a water-soluble highly conducting polythiophene derivative. This material, PEDOT-S, has shown affinity for amyloid fibrils, but can also be very useful in conventional opto-electronic polymer-based devices.
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- Herland, Anna, 1979-, et al.
(författare)
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Conjugated polymers as optical probes for protein interactions and protein conformations
- 2007
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Ingår i: Macromolecular rapid communications. - : Wiley. - 1022-1336 .- 1521-3927. ; 28:17, s. 1703-1713
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for highly sensitive, multi-parallel protein sensors within diagnostics and proteomic research. Conjugated polymers (CPs) have been demonstrated as highly sensitive optical probes for protein biosensing. Compared to small molecules, the polymeric probe has the possibility of multiple interactions and a collective response, which enhances the sensor signal. The optical output is colorimetric or, more sensitive, fluorescence based, including Förster energy transfer and changes in the emission wavelengths and/or intensity. Using CPs, many interesting protein detection events have been demonstrated, e.g., protein interactions, enzymatic activity, amyloid fibril formation, and detection by aptamers. CPs have also been successfully used to stain bacterial, cellular, and tissue samples. © 2007 WILEY-VCH Verlag GmbH & Co. KGaA.
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- Nilsson, Peter, et al.
(författare)
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Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
- 2007
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
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- Yasuga, Hiroki, et al.
(författare)
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Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds
- 2021
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Ingår i: Nature Physics. - : Springer Nature. - 1745-2473 .- 1745-2481. ; 17:7, s. 794-800
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Tidskriftsartikel (refereegranskat)abstract
- Structures that are periodic on a microscale in three dimensions are abundant in nature, for example, in the cellular arrays that make up living tissue. Such structures can also be engineered, appearing in smart materials(1-4), photonic crystals(5), chemical reactors(6), and medical(7) and biomimetic(8) technologies. Here we report that fluid-fluid interfacial energy drives three-dimensional (3D) structure emergence in a micropillar scaffold. This finding offers a rapid and scalable way of transforming a simple pillar scaffold into an intricate 3D structure that is periodic on a microscale, comprising a solid microscaffold, a dispersed fluid and a continuous fluid. Structures generated with this technique exhibit a set of unique features, including a stationary internal liquid-liquid interface. Using this approach, we create structures with an internal liquid surface in a regime of interest for liquid-liquid catalysis. We also synthesize soft composites in solid, liquid and gas combinations that have previously not been shown, including actuator materials with temperature-tunable microscale pores. We further demonstrate the potential of this method for constructing 3D materials that mimic tissue with an unprecedented level of control, and for microencapsulating human cells at densities that address an unresolved challenge in cell therapy.
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